Anti-opioid effects of neuropeptide FF receptors in the ventral tegmental area

The present study investigates the modulatory effects of neuropeptide FF (NPFF) receptors on the mesolimbic dopaminergic pathway controlled by opioid receptors. A stable NPFF2 receptor agonist, dNPA, was injected into the ventral tegmental area (VTA) and the release of dopamine and serotonin within the nucleus accumbens (NAc), induced by intraperitoneal injection of morphine, was monitored using the brain microdialysis, in non-constrained rat. dNPA decreased systemic morphine-induced elevation of dopamine and serotonin metabolites within the NAc. Furthermore, co-injected with morphine into the VTA, NPFF inhibited morphine-induced stereotypy 60–120 min after the injection. This neurochemical and behavioural anti-opioid effect mediated by NPFF2 receptors at the level of VTA suggests the involvement of NPFF in the rewarding effects of opiates on the mesolimbic dopamine system.

Research highlights▶ Neuropeptide FF receptors control opioid activity. ▶ Morphine induced elevation of monoamine levels within the nucleus accumbens. ▶ NPFF2 receptors in the ventral tegmental area inhibited this increase. ▶ NPFF2 receptors inhibited morphine-induced stereotypy.